Neutron capture therapy (NCT) is a unique form of radiation due to the combination of high linear energy transfer (LET) properties and biological targeting. Extensive preclinical work and early clinical experiences have shown NCT to be active against melanoma, a disease poorly controlled by conventional radiation. This phase II trial is designed to establish an unambiguous proof-of-principle for NCT by producing a measurable clinical response, defined as a complete response (CR) or partial response (PR, greater than or equal to 50 percent reduction in the greatest diameter of disease), within an acceptable level of acute and chronic dermal reaction. The long-term objective is to integrate NCT into the established therapeutic mainstream for melanoma and other malignancies. Boron-delivery will be through the use of l-p-boronophenylalanine-fructose (BPA-f), 14 grams/meter-squared IV, over 90 minutes. Neutron irradiation will take place at the newly constructed fission converter beam (FCB) and proposed thermal neutron facilities at MIT. A minimum biologically weighted dose of 24 RBE-Gy will be prescribed to the clinical tumor volume (cTV) while not exceeding a dermal dose of 16.7 RBE-Gy, a dose already determined in previous trials to be within tolerance. A total of 36 patients with measurable disease 6 cm or less in depth and <10 cm in diameter will be enrolled over 3 years. 10B will be quantified in blood, skin and tumor using established nuclear analytic methods. The tumor response will be objectively evaluated clinically and histopathologically. The following are the specific research objectives for the 3-year period: (1) To examine, through serial objective measurements, the clinical response of melanoma following a specified minimum tumor dose of NCT. (2) To determine the time course, uniformity and severity of acute dermal reactions following NCT. (3) To characterize the late dermal reactions in patients who have been followed for at least six months post-NCT. (4) To measure the 10B distribution in tumor and normal tissue, using sophisticated macroscopic and microscopic nuclear analytic methods in order to validate the 10B concentrations currently used for dosimetry. (5) To further the level of understanding of the pharmacokinetics of BPA-f, through measurement of blood and plasma concentrations of 10B and determination of the glomerular filtration rate. These data will be used to refine the predictive accuracy of a two-compartment pharmacokinetic model developed by this research group from human clinical data.